Iranian Journal of Pharmaceutical Research (2016), 15 (4): 677-686 Copyright © 2016 by School of Pharmacy Received: Jan 2016 Shaheed Beheshti University of Medical Sciences and Health Services Department of Pharmaceutics Accepted: Jan 2016

Original Article

Formulation and Taste Masking of Ranitidine Orally Disintegrating Tablet

Zahra Hesaria, Akram Shafieeb, Shirin Hooshfarc, Naser Mobarrad and Seyed Alireza Mortazavic*

aDepartment of Pharmaceutics, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran. bDeptartment of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran. cDepartment of Pharmaceutics School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. dStem Cell Research Center, Department of Biochemistry, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

Abstract

Orally Disintegrating Tablets (ODT) have the advantages of both solid dosage form specially the stability and ease of handling and liquid dosage forms including ease of swallowing and pre-gastric absorption. We focused on taste masking and formulation of ranitidine ODT which disintegrates rapidly in the mouth within 60 sec using super-disintegrants, special polymers, water soluble and even insoluble excipients, sweeteners and essence. Various formulations were designed and made in four series. The amount of ranitidine in each formulation was 150 mg, and the final weight of tablets was around 500 mg. Prepared formulations were evaluated in terms of several physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Several taste masking techniques were investigated in each series of formulation, in order to cover the bitter taste of wranitidine. These included the addition of sweetener, granulation, solid dispersion with soluble and insoluble agents and complex formation with cellulose derivatives. The best formulation(s) in each group was/were chosen for taste evaluations with the help of 10 volunteers. Finally, formulation F14 was selected as the ultimate formulation, based on its better taste and shorter disintegration time (around 5 seconds). Formulation F14 contained Na CMC, avicel, Na starch glycolate, xylitol, saccharin, Na benzoate and menthol. The chosen formulation successfully passed the complementary evaluations such as assay of active ingredient and dissolution time. Na CMC was found to be acceptable in terms of decreasing disintegration time and enhanced taste masking potential and can be used in further ODT formulations.

Keywords: Orally Disintegrating Tablets (ODT) ; Ranitidine HCl; Taste masking; Sodium CMC; Xylitol.

Introduction discovered advanced information about the physicochemical and biochemical parameters Since pharmaceutical scientists have relevant to their profession, drug delivery systems have been increasingly promoted over * Corresponding author: the past decades (1). E-mail: [email protected] Recently, patient-friendly dosage forms are Hesari Z et al. / IJPR (2016), 15 (4): 677-686 growing higher interests among pharmaceutical unavoidable criteria for formulation (13-15). companies and medical society members in Ranitidine is a histamine H2-receptor addition to patients. Most of therapeutic agents antagonist that inhibits stomach acid production. considered for systemic drug delivery have It is commonly used in the treatment of peptic a tendency to be administered via oral route, ulcer and gastro-esophageal reflux disease. owing to their numerous advantages, particularly Certain preparations of ranitidine are greater patient compliance due to their ease of available over the counter (OTC) in various administration. Among these dosage forms are countries. It is on the World Health Organization›s the orodispersible or orally disintegrating tablets List of Essential Medicines, the most important (ODT) (2, 3). medications needed in a basic health system An ODT is a solid dosage form that (16). disintegrates and dissolves in the mouth without Ranitidine HCl has a bitter taste and sulfur- water within 60 seconds or less. The US Food like odor (17). Various taste masking techniques and Drug Administration Center for Drug such as addition of sweeteners and flavors (18), Evaluation and Research (CDER) has a definition filling in capsules, coating with water insoluble in the Orange Book an ODT as ″A solid dosage polymers or lipids (19), adsorption to ion- form containing medicinal substances, which exchange resin,complexing with cyclodextrin disintegrates rapidly, usually within a matter of (20), have been employed for masking its bitter seconds, when placed upon the tongue” (4). The taste in order to increase patient compliance. European Pharmacopoeia however similarly In addition to conventional formulations of defines: orodisperse, as a tablet that can be Ranitidine, existing in the market, AashimaHooda placed in the mouth where it disperses rapidly et al. developed gastro-retentive microspheres before swallowing (5). Over the past three using chitosan as a drug delivery carrier which decades, ODTs have attracted much interest as a extended drug release by zero order kinetic for delegated alternative to conventional oral dosage 10 h (21).Kavitha and co-workers prepared forms such as tablets and capsules (6). Ranitidine floating tablets using Hydroxy Propyl Certain studies concluded increased Methyl Cellulose (HPMC). This formulation bioavailability and proved rapid absorption prolonged the floating and drug release time of drugs through pre-gastric absorption from to 24 h (22).On the other hand, Mannur et al. mouth, pharynx & esophagus, as saliva passes developed a ranitidine fast disintegrating tablet down, therefore rapid onset of action and with the use of various super disintegrants increased bioavailability will be expected (7). such as sodium carboxy methyl cellulose (Na Moreover, protection from hepatic first pass CMC), pregelatinised starch and sodium starch effect provides higher bioavailability, which is glycolate (SSG), in addition to mannitol and very considerable for reduction of drug dose and aspartame for improving the mouth feel and accordingly its related side effects (8). taste. Disintegration time ranged between 19-22 The target communities in ODT consumption s and Na CMC containing formulations showed are children, the elderly, hospitalized patients, superior organoleptic properties (23). In a bodily and mental cripples, those with separate study, Rishikesh et al. developed a fast mastication and deglutition problems, patients disintegrating tablet with the use of ranitidine with resistant chronic nausea, patients under as the model drug. They did not use any taste chemotherapy, psychotic patients who hide their masking agent to cover the bitter taste of drug, tablets beneath their tongue and those people or which seems unpracticable in ODT market. They travelers who have no access to water. ODTs incorporated two superdisintegrants including have also been recently used in animals (9-11). Kollidon CL and SS. Tablets containing Whereas ODTs are going to disintegrate Kollidon CL showed faster disintegration time in the buccal cavity and in direct contact with (25-30 sec) and the percentage of drug release tongue’s taste buds (12), pleasant mouth feel and (90% in 15 min) was also higher than the other masking the naturally bitter taste of most active superdisintegrants investigated (24). pharmaceutical ingredients (APIs) is one of the The aim of this study was to develop a new

678 Ranitidine orally disintegrating tablet

Ranitidine ODT formulation, putting emphasis also contained 150 mg ranitidine (active on improved taste masking of this bitterly tasted ingredient), 150 mgavicel (filler), 30 mg sodium drug, using different approaches. starch glycolate (super-disintegrant), 30 mg Na benzoate (flow aid), 83.5 mg of each of xylitol Experimental and saccharin (sweeteners) and 5 mg menthol for masking the sulfur like odor. Materials In series B formulations, drug powder was Ranitidine HCl powder was purchased from granulated with PEG 4000, using the solid Sacara Co. (India). Xylitol (pharmaceutical dispersion method. In here the water soluble grade), sodium saccharine (food grade: FAD polymer PEG 4000 was melted using the bain- 8), sodium starch glycolate (SSG) (primojel), marie technique and mixed with equal amount sodium benzoate, poly ethylene glycol (PEG of drug powder and was then cooled down to a 4000) and menthol all were purchased from semi solid state. Next, it was passed through a 30 Merck (Germany). Croscarmellose was obtained mesh sieve and formed into granules in order to from FMC Biopolymer (Ireland), Na CMC grade lessen the drug powder contact with taste buds. 30000, HPMC and Poly vinyl pyrrolidone 10 It is also hypothesized that PEG can temporarily (PVP 10) were all obtained from sigma (USA). and partially cover the drug particles to lessen the bitter taste sensation. Granules were then Preliminary studies on ranitidine powder used in different formulations, alongside the First, physicochemical properties of ranitidine sweeteners and menthol, as presented in Table 1. powder were investigated such as powder purity, In Series C formulations, drug powder organoleptic properties (color, texture, taste was granulated with white wax, using solid and smell) and flowability (by measuring the dispersion method. In the next step granulation Carr’s index and Hussner’s ratio). Moreover, with white wax was performed with the same compressibility and disintegration time of the method of PEG. Due to its lower water solubility, compressed drug powder was evaluated. it’s supposed that drug release will decrease in oral cavity and bitter taste will be sensed less. Formulation of ranitidine orally Four formulations were designed alongside with disintegrating tablets sweeteners and menthol as shown in Table 2. Due to ranitidine’s bitter taste, its’ ODT In series D formulations, ranitidine was formulation requires challenging taste masking complexed with the cellulose-based polymer strategies. In this study we were looking for sodium carboxymethyl cellulose (NaCMC), in simple industrially operative strategies. First, a order to coat drug particles with the polymer. basic formulation was designed and prepared for NaCMC was hydrated with water to form a gel ranitidine ODT, containing avicel as the filler, with a viscosity of about 70 cps. Next, the drug sodium starch glycolate as the super-disintegrant powder was added to the gel and the mixture was and sodium benzoate as the water soluble dried in a vacuum oven at 50 °C for two hours. lubricant. The direct compression method, The dried gel was triturated and passed through alongside the granulation technique in some a 30 mesh sieve. Different ratios of polymer to formulations, was applied for tablet preparation drug were prepared, also containing sweetener and four series of taste masked formulations and menthol. Formulations prepared have been were prepared. shown in Table 3. In series A formulations, sweeteners and essence were added to formulation. Based on Physicochemical evaluations of ranitidine previous investigations, saccharin and xylitol ODT formulations are among the sweeteners which are widely Different ranitidine ODT formulations used for masking the bitter taste, at a ratio of prepared, underwent physicochemical tests 1:1 or 1:2, mainly due to their non-glycogenic mentioned below: characteristic which is ideal for use in pediatric (I) Power/granule flowability: and diabetic patients (25). Series A formulation flowability was measured in terms of

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Table 1. Series B ranitidine ODT formulations, prepared using PEG 4000 and the solid dispersion technique. Intra- granular components (mg) Extra- granular components (mg) Na Formulations Ranitidine PEG 4000 Avicel Avicel SSG Xylitol Saccharin Menthol benzoate F2 150 150 _ 100 40 _ _ _ 40 F3 150 150 _ 100 _ _ _ 20 F4 150 150 _ 150 _ _ _ _ _ F5 150 150 50 100 _ _ _ _ _ F4a 150 150 _ 100 45 60 30 10 5 F4b 150 150 _ 145 _ 60 30 10 5

calculating the Carrꞌs index [(C = 100(1-ρB/ to the wall of a beaker containing 10 mL pH

ρT)],where ρB is the freely settled bulk density of 7.2 phosphate buffer (same as the saliva’s pH). the powder, and ρT is the tapped bulk density of Then, the beaker was placed on a shaker with the powder) and Hausnerꞌs ratio (H = ρT/ ρB). a speed of 30 rpm, for imitation of light flow )II) Tablet appearance: of saliva. The duration of time required for tablets should have a flat and smooth surface, disintegration of each tablet was recorded. This with no chipping, cracking or any other defect. test was performed at room temperature. (III)Thickness: a digital vernier caliper was employed for Taste masking and complementary tests on measuring tablet thicknessin mm. the selected formulations (IV) Uniformity of weight: Formulations which showed optimum this was determined by weighing 20 physicochemical properties, were found to be randomly selected tablets. acceptable for further studies. They underwent (V)Hardness: additional studies, as follows: Hardness of tablets was determined using a (I)Consumer’sacceptance: Monsanto hardness tester, and expressed in kp. Ten healthy and non-smoking volunteers; (VI) Friability: 5 females and 5 males, aged between 20 to 29 Friability of the tablets was examined, using years; took part in this study and expressed aRoche friabilator and was expressed in %. their opinion on the appropriateness of the (VII) Disintegration time: taste of selected formulations. This was based an ODT formulation should disintegrate or on a scale from 1 to 5, with 1 representing the dissolve in water quickly. Hence, for conducting worst formulation and 5 the best formulation. It the disintegration time test, 6 tablets from each should be mentioned that the test formulations formulation were chosen randomly and each were coded in order to prevent any bias in individually dropped into a basket connected the volunteers. Following the comparison of

Table 2. Series C ranitidine ODT formulations, prepared using white wax and the solid dispersion technique. Intra- granular components (mg) Extra- granular components (mg) Na Formulations Ranitidine White wax Avicel Avicel SSG Xylitol Saccharin Menthol benzoate F6 150 150 _ 150 50 _ _ _ 5 F7 150 100 _ 150 90 60 30 10 6 F8 150 100 100 144 _ 60 30 10 6 F9 150 150 150 _ 60 50 20 10 6

680 Ranitidine orally disintegrating tablet

Table 3. Series D ranitidine ODT formulations, prepared using complexation between the drug and Na CMC. Intra- granular components (mg) Extra- granular components (mg) Na Formulations Ranitidine Na CMC Xylitol Saccharin Avicel SSG Xylitol Saccharin Menthol benzoate F10 150 50 _ _ 155 90 _ _ _ 5 F11 150 100 _ _ 95 50 60 30 10 5 F12 150 50 _ _ 145 50 60 30 10 5 F13 150 50 _ _ 115 80 60 30 10 5 F14 150 50 _ _ 185 60 60 30 10 5 F15 150 50 20 10 135 60 40 20 10 5

the taste of formulations, the most suitable randomly, and 500 mg (equal to 1 tablet) was formulation was considered as the ultimate weighted to be assayed. The powder was formulation. This formulation was studied in dissolved in mobile phase at a concentration of terms of supplementary physicochemical tests. 0.112 mg/mL, same as the standard solution, and (II) Assay of active ingredient: passed through a 0.22 µM filter and then injected HPLC was used for this test. The column was into the HPLC injection port (26). Finally, with C18 and the mobile phase consisted of aqueous the use of area under the curve (AUC) of the ammonium acetate: methanol (85:15 v/v) with peaks and the calculations mentioned in USP, a flow rate of 1.5 mL/min. A UV detector was the amount of ranitidine present in ODTs and employed for detection of ranitidine in the standard samples were calculated and compared. wavelength of 322nm. 20 tablets were powdered (III) Dissolution time test:

Table 4. The results of physicochemical evaluations on series A, B, C and D of ranitidine ODT formulations (results are presented as mean ± standard deviation). Uniformity of Flowability Appearance Thickness Hardness Friability Disintegration Formulation weight (n=3) (n=10) (mm, n=10) (KP, n=10) (%, n=1) time (n=6) (mg, n=20) F1 Good Desirable 3.03±0.18 505.34±0.11 3.55±1.87 34 > 60 s F2 Excellent Undesirable 2.88±0.02 445.96±1.23 4.55±0.57 45 > 60 s F3 Excellent Undesirable 2.48±0.01 420.63±1.13 4.70±1.00 59 > 60 s F4 Moderate Desirable 3.08±.03 450.26±1.68 4.08±0.25 68 21.83±6.56 F4a Moderate Undesirable 3.16±0.02 549.59±1.47 4.46±0.50 43 > 60 s F4b Good Desirable 3.30±0.02 549.97±1.27 4.09±0.49 42 20.33±3.98 F5 Moderate Desirable 2.95±0.01 452.62±2.63 3.77±0.45 57 > 60 s F6 Good Desirable 3.43±0.01 503.54±1.09 3.19±0.21 37 > 60 s F7 Moderate Desirable 3.33±0.01 593.53±1.77 3.42±0.16 14 > 60 s F8 Good Undesirable 3.35±0.01 600.06±1.14 3.71±0.32 18 > 60 s F9 Excellent Undesirable 3.33±0.01 592.58±1.65 3.45±0.15 5 > 60 s F10 Moderate Desirable 2.95±0.02 455.27±1.35 7.19±0.45 43 25.67±5.32 F11 Moderate Desirable 2.96±0.02 498.46±1.45 1.93±0.09 Chipped _ F12 Moderate Desirable 2.95±0.03 496.86±2.11 7.56±0.67 7 20.17±6.18 F13 Excellent Desirable 2.98±0.02 496.98±2.07 7.16±0.81 56 28.33±5.61 F14 Moderate Desirable 3.14±0.01 550.12±1.58 8.65±0.39 8 5.17±2.14 F15 Excellent Desirable 2.98±0.01 501.09±1.17 7.38±0.45 59 15.69±4.18

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dissolution test was performed on 10 tablets, method. Disintegration time of compacted using the paddle system in distilled water powder discs was over 10 min indicating the medium, at a speed of 50 rpm for 45 min based need for the inclusion of effective disintegrants on the USP guideline (27). A UV detector was in formulation. employed for the determination of ranitidine concentration in water at different time intervals, Ranitidine ODT formulations following the construction of a calibration curve. Various formulations were prepared using different ingredients in four series (A-D), and Statistical analysis physicochemical properties of each series For the purpose of comparison between two including flowability, appearance, thickness, different test samples, independent sample t-test uniformity of weight, hardness, friability and was used and for more than two samples, one disintegration time were investigated. The way ANOVA was utilized. In cases in which results obtained have been shown in Table 4. significant differences existed in the ANOVA Flowability of all formulations was improved test, Tukey post-hoc test was used to specify in comparison with the ranitidine powder, due those samples having significant differences with to the addition of property modifying excipients each other. In qualitative samples (taste studies), such as sodium benzoate (ANOVA, p < 0.05). Friedman and Wilcoxon paired statistical In series A formulation the disintegration time test was used. The Friedman test shows the was longer than 60 sec and also the addition existence of an overally significant difference of the sweeteners could not mask the bitter between formulations and the Wilcoxon paired taste completely. Therefore, F1 formulation test compares formulations with each other pair- was omitted from further complementary wise, in order to specify samples with significant evaluations. In series B formulations, only the differences. In all the above mentioned tests, a F4 formulation had a disintegration time of less p-value ≤0.05 was considered as significant. than 60 sec (21.83 ± 6.56 s). Formulation F4 was a basic formulation, Results merely formed by granulating the drug with PEG4000, and did not contain any sweetener The results obtained from the studies or essence. Hence, formulations F4a and F4b conducted on ranitidine powder and the various were designed and made using xylitol, saccharin ranitidine ODT formulations prepared, have and menthol. Based on the results, formulation been presented as follows: F4b had a desirable appearance and quicker disintegration time than formulation F4a, and Preliminary studies on ranitidine powder was therefore chosen for further evaluations. At first physicochemical characteristics of In series C formulations in which white wax ranitidine powderwas examined, including the was utilized for taste masking, none of the organoleptic characteristics, powder flowability, formulations had an appropriate disintegration compressibility and disintegration time. time, but formulation F7 had a desirable Results showed that ranitidine is a yellowish appearance and moderate flowability and hence powder with undesirable bitter taste and sulfur- was selected for complementary studies. In the like odor, complying with the specifications. last series of formulations (series D),in which The results obtained for flowability, based on NaCMC was incorporated for masking the bitter the Carrꞌs index and Hausnerꞌs ratio, showed taste, the disintegration time was impressively poor powder flow which needs the addition of decreased to nearly below 30 s (ANOVA, p < appropriate lubricants for modification. 0.05) and the tablet appearance was desirable in The maximum amount of powder all formulations. Formulations F14 and F15 were compressibility, following the preparation of chosen due to their lower disintegration times compressed powder discs was 3.12 ± 0.46 KP (n for complementary evaluations. The selected = 10), showing an acceptable degree of powder formulations physicochemical test results are compressibility for the direct compression shown in Figure 1.

682 Ranitidine orally disintegrating tablet

Figure 1. Comparative results of physicochemical tests carried out on the selected ranitidine ODT formulations, including the mean disintegration time (n = 6), mean hardness (n = 10) and % of friability (n = 1).

Complementary studies on the selected Na benzoate, xylitol, saccharin and menthol formulations underwent additional physicochemical tests, Formulations F4b, F7, F14 and F15 including the assay of active ingredient and were subjected to taste masking evaluation. dissolution time. Formulation F14 was found Following the comparison of the scores given to contain103.2±4.99 % (mean ± standard by ten volunteers to the tastes of the selected deviation; n = 3) ranitidine HCl, based on the formulations, formulation F14 was chosen as assay of active ingredient test, which complied the ultimate formulation (Figure 2. shows the with the acceptable limit of 90.0-110.0% scores from 1 to 5). Statistical studies showed mentioned in the literature(26). a significant difference between formulation When examining the dissolution profile F14 and the other three formulations (Wilcoxon (time) of formulation F14, more than 85% of its’ test, p < 0.05). Formulation F14 which drug content was released over a period of 45 contained ranitidine HCl complexed with minutes, which is within the acceptable range NaCMC, alongside avicel, Na starch glycolate, stated in the literature(27).

Figure 2. Taste score of selected ranitidine ODT formulations (scoring scale: the worst = 1 and the best = 5; n = 10).

683 Hesari Z et al. / IJPR (2016), 15 (4): 677-686 Drug Dissolved (%)

Figure 3. The dissolution profile of ranitidine ODT formulation F14 in distilled water (results presented as mean ± standard deviation, n = 3).

Discussion of higher amounts of filler (avicel) can help to decrease the sticky property of the formulation. Ranitidine is an oral drug that is widely used In the other hand, the hydrophobic characteristic as an effective H2 antagonist and blocks the of white wax may reduce water penetration into production of acid by acid-producing cells in the tablet matrix, and this can subsequently the stomach. It is commonly used in treatment make the disintegration time longer. In series D of peptic ulcer disease and gastroesophageal formulations, the difference in flowability was reflux disease, which are prevalent nowadays significant among the investigated formulations in all ages especially elderlies. In this study we (ANOVA and Tukey Post-Hoc test, p < 0.05). aimed to design a novel and simple ranitidine Formulation F10 was a basic formulation and ODT formulation, using polymers, water- had a moderate flow, while formulations F13 soluble excipients and super-disintegrants. These and F15 both had excellent flows. In these two formulation strategies could be cost-beneficial formulations the presence of lower amounts and can be easily adopted in industrial scale in of avicel in the extra-granular part of these the pharmaceutical companies. formulations seems to be the reason for their Generally speaking in ODT formulations, better flowabilities. In formulation F11 the disintegration time and taste masking are weight of NaCMC was twice that of the other the two most important issues which should formulations. Therefore, the compressibility of be considered in their formulation design this formulation decreased and its’ maximum (28). In series B formulations although F2 achieved hardness was less than 2 Kp and the and F3 formulations had better flowabilities, produced tablets did not pass the friability test. formulation F4 was selected for further taste All the series D formulations had significantly masking studies due to its better appearance lower disintegration times compared to series and lower disintegration time (21.83±6.56) A, B and C formulations (ANOVA and Tukey (ANOVA, p < 0.05). It seems that the presence Post-Hoc test, p < 0.05). Formulation F14 of higher amounts of Na benzoate as a flow aid had the lowest disintegration time (about 5 in formulations F2 and F3 was the reason for sec), which was significantly different from their better flowability. In series C formulations, the other formulations in series D (ANOVA formulations F8 and F9 were too sticky, which and Tukey Post-Hoc test, p < 0.05). This is led to an undesirable tablet appearance. Presence presumably due to the higher amount of avicel

684 Ranitidine orally disintegrating tablet present in this formulation, which has a strong dissolution. disintegration property and also the presence Overall, based on the physicochemical tests of NaCMC with potential property as a super- conducted as well as the taste masking studies, disintegrant. Moreover, the presence of NaCMC formulation F14 seems to be the most suitable alongside sodium starch glycolate could provide formulation for the preparation of ranitidine ODT. a synergistic effect in terms of decreasing the disintegration time. In the taste masking studies it Conclusion was found that NaCMC can mask the bitter taste and sulfur-like odor of ranitidine to an acceptable In this study we aimed to formulate a novel taste masking can be the result and simple ranitidine orally disintegrating ׳extent. In here of ionic complex formation between ranitidine tablet, capable of disintegrating rapidly within HCl molecules and the ionic NaCMC chains, the buccal cavity. The ultimate ranitidine ODT resulting in salt formation. In addition, the use of formulation selected was formulation F14, xylitol and saccharin at a ratio of 2:1, resulted in which contained ranitidine and NaCMC as the a fine sweet taste in the mouth. Furthermore, the intra-granular components and xylitol alongside presence of menthol created a sense of coolness saccharin and menthol, avicel, sodium starch and freshness within the mouth, as well as a glycolate and Na benzoate as the extra-granular sweet and cool after taste in the mouth. The use components. This formulation complied well of these sweeteners has been reported to be useful with all the physicochemical tests conducted, in ODT formulations. Rishikesh et al. developed particularly disintegrating within 5 sec. In a new fast disintegrating tablet with ranitidine addition, this formulation also provided a as the model drug (24). They also incorporated desirable taste and after taste within the buccal Kollidon CL and sodium starch glycolate as cavity and hence could be considered as an super-disintegrant. The point to note in this appropriate ODT formulation for ranitidine. study is that although they reached an acceptable disintegration time (25-30 s), no taste masking References strategy was adopted in this study to cover the bitter taste of ranitidine. Hence, this formulation (1) Hirani JJ, Rathod DA and Vadalia KR. Orally cannot be looked upon as a desirable formulation disintegrating tablets: A review. Trop. J. Pharm. Res. for use in patients. In a different study Mannur (2009) 8: 161-72. et al. designed a ranitidine fast disintegrating (2) Sastry SV, Degennaro MD, Reddy LK and Khan MA. Atenolol gastrointestinal therapeutic system. I. tablet, in which they used different super- Screening of formulation variables. Drug. Dev. Ind. disintegrant including sodium starch glycolate, Pharm. (1997) 23: 157-65. pregelatinized starch and NaCMC (23). They (3) Nagar P, Singh K, Chauhan I, Verma M, Yasir M, Khan succeeded to decrease the disintegration time A, Sharma R and Gupta N. Orally disintegrating tablets of tablet to 19-22 s. However, they incorporated : Formulation, preparation techniques and evaluation. J. Appl. Pharm. Sci. (2011) 1 (4): 35-45. NaCMC just as a super-disintegrant, and declared (4) FDA UFaDA. Cder data standards manual. (2003) that NaCMC containing formulations can show (5) EP. European pharmacopoeia. 5th eddition. Strasbourg, better organoleptic properties. Our study is in France. (2005) 5: 628. agreement with this study, regarding both the (6) Shankarrao KA, Mahadeo GD and Balavantrao super-disintegration and taste making properties KP. Formulation and in-vitro evaluation of orally of NaCMC. disintegrating tablets of olanzapine-2-hydroxypropyl- β-cyclodextrin inclusion complex. Iran. J. Pharm. Res. As shown in Figure 3. the amount of drug (2010) 9: 335-47. released from the selected formulation F14 was (7) Brown D. Orally disintegrating tablets - taste over 91.2% after 45 min, and over 86.5% after 30 speed. Drug Develop. Deliv. (2003) 3: 2-3. min. It seems that the presence of NaCMC in (8) Rangasamy M, Ayyasamy B, Raju S and Gummadevelly tablet formulation could help to increase water S. Design and evaluation of the fast dissolving tablet of terbutaline sulfate. Asian J. Pharm. (2009) 3: 215-7. penetration and uptake into the tablet matrix. (9) Saljoughian M. Atypical antipsychotics: Safety and use This can subsequently result in an improved in pediatric patients US Pharmacist. (2015) 40: 52-5. tablet disintegration and faster drug release and (10) Kearney P. Modified release drug delivery technology.

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